The human T-cell lymphoma virus, HTLV-I, is thought to be directly associated with adult T-cell leukemia (ATL) and indirectly associated with other malignancies. More recently this virus has been shown to be associated with the neurologic disease, tropic spastic paraparesis (TSP). Studies are underway to examine the mechanism whereby the same virus appears to contribute to different types of diseases. Peripheral blood lymphocytes from HTLV-I seropositive individuals with the neurologic disease have been shown to undergo spontaneous proliferation when placed in culture. We have undertaken experiments to assess the nature of the lymphocyte population that is proliferating and the mechanism whereby this response is induced. Lymphocytes from HTLV-I-infected and noninfected individuals were tested prior to and after 6 days of culture for cell-surface markers that define activated lymphocyte subpopulations. HTLV-I seropositive disease-free individuals had a relatively normal distribution of lymphocyte subpopulations. After 6 days of culture the subpopulation of CD4 cells expressed activation markers, human leukocyte antigen (HLA)-DR and interleukin (IL)-2. This population of lymphocytes from TSP patients appeared activated prior to culture. Supernatants from these cultures were assayed for cytokines, IL-1-alpha, IL-1beta, IL-2, IL-4, IL-6, granulocyte-macrophage-colony stimulating factor, and tumor necrosis factor (TNF). Elevated levels of IL-6 were observed in the cultures of lymphocytes from HTLV-I-infected individuals regardless of disease states. TNF was absent in the lymphocyte cultures from any of the infected individuals. Other cytokines were present in the culture but did not tend to differentiate with disease category.